Levetiracetam in pregnancy: encouraging findings
For women with epilepsy, seizure control during pregnancy is very important; however exposure to some anti-epileptic drugs (AEDs) can be harmful to babies’ development. Pregnancy planning for these women therefore comes with some very difficult decisions, and they need to be given thorough advice from a specialist.
A number of studies have investigated specific AEDs for adverse effects, but so far an ‘ideal’ drug for pregnancy has not been found. Even if it had it wouldn’t benefit everyone, of course, because some women would be unresponsive to it. There are still many unknowns in this area, and this makes decision making particularly challenging.
So what do we know about AEDs and pregnancy? Here is a very broad summary of the evidence to date:
Exposure to older AEDs such as phenobarbital, phenytoin, carbamazepine and (in particular) sodium valproate have been shown to increase the risk of major birth defects including spina bifida and cleft lip/palate. This has not been found to be the case for newer AEDs such as lamotrigine, oxcarbazepine, topiramate, gabapentin and levetiracetam; although there may still be a risk of smaller birth defects because this hasn’t yet been explored.
A number of studies have also linked exposure to sodium valproate in the womb (but not to phenytoin or carbamazepine) to a risk of delayed language and cognitive development (and unsurprisingly medical guidelines recommend that sodium valproate is avoided during pregnancy if at all possible). The relevant data is currently lacking for many of the newer AEDs, although lamotrigine has been studied and is reportedly ‘safe’. Unfortunately, however, lamotrigine has been linked to an increased risk of seizures during pregnancy (the implications of which to unborn child are yet to be investigated).
The current study
Levetiracetam is quite often recommended by specialists for pregnancy, but there is in fact insufficient reliable data to make this recommendation. To address this, researchers in Liverpool and Belfast recently explored the effects of levetiracetam exposure on later cognitive and language development. They compared this to the development of children born to women without epilepsy who did not take any medication during pregnancy (the controls). The team also assessed children born to women who took sodium valproate during pregnancy for comparison with the levetiracetam group.
The study recruited a total of 248 children aged between 3 and 4.5 years from across the UK. Fifty-three of the children had been exposed to levetiracetam in the womb, 44 had been exposed to sodium valproate and 151 were controls. The cognitive and language abilities of all of the children were assessed using standard scales of measurement – the Griffiths Mental Development Scales and the Reynell Language Development Scale. On these scales, scores corrected for age run from 50-150, with 85-115 being the ‘normal range’. The average scores from each group were calculated (for every assessment), and statistical methods were used to make the relevant comparisons.
When the results were analysed, the team found that children exposed to levetiracetam before birth did not differ from the controls in any of the tests performed. Unsurprisingly, therefore, when the sodium valproate and levetiracetam groups were compared, the sodium valproate group scored, on average, 15.8 points lower for gross motor ability (the ability to control large muscle groups required for walking, running, sitting etc), 6.4 points lower for language comprehension and 9.5 points lower for language expression.
These results are very welcome, because they suggest that taking levetiracetam during pregnancy does not put the unborn child’s cognitive or language development at risk. Taken with previous evidence (that levetiracetam is not linked to major birth defects), this is extremely encouraging for young women who are responsive to levetiracetam. More research needs to be done to check that levetiracetam doesn’t have other adverse effects to those already studied; however specialists should use this new information when helping women with epilepsy to plan their pregnancies.